Functional consequences of noncognate interactions between CD4+ memory T lymphocytes and the endothelium
Functional consequences of noncognate interactions between CD4+ memory T lymphocytes and the endothelium
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DOI：
10.4049/jimmunol.168.7.3227
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发表时间：
2002-04-01
影响因子：
4.4
通讯作者：
Marelli-Berg, FM
中科院分区：
文献类型：
--
作者：
Berg, LP;James, MJ;Marelli-Berg, FM
将Ag特异性T细胞募集到炎症部位是免疫监视的关键步骤。尽管控制T细胞外渗的分子相互作用的特征相对较好，但这些事件对T细胞功能的影响仍然知之甚少。使用人CD 4（+）记忆T细胞跨内皮迁移的体外模型，我们研究了与内皮接触的T细胞中诱导的分子和功能变化。首先，我们表明，跨内皮细胞迁移是排除信号，导致T细胞分裂。此外，在与内皮细胞（EC）非同源相互作用后，在T细胞中观察到转录因子AP-1的激活，而不诱导NF-κ B，这是一种不同于在分裂T细胞中观察到的转录调控模式。某些粘附（CD 11 a，CD 49 d），活化（CD 69）和共刺激（CD 86）受体的上调伴随着这些转录事件。最重要的是，最近迁移的T细胞显示出更快的迁移率时，重新贴附到EC单层。最后，T细胞与内皮细胞发生非同源相互作用后，对抗原攻击反应过度。这些效应似乎不是由于预活化T淋巴细胞的选择，因为它们也发生在克隆T细胞群中，并且似乎是由α（L）β（2）整合素-CD 54相互作用介导的。我们的结论是，CD 4（+）记忆T细胞外渗伴随着与EC的相互作用诱导的表型和功能的变化，这有利于组织浸润的T细胞和它们的进一步激活，一旦它们到达抗原位点。
The recruitment of Ag-specific T cells to sites of inflammation is a crucial step in immune surveillance. Although the molecular interactions controlling T cell extravasation are relatively well characterized, the effects of these events on T cell function are still poorly understood. Using an in vitro model of transendothelial migration of human CD4(+) memory T cells, we have investigated the molecular and functional changes induced in T cells that come into contact with the endothelium. First, we show that transendothelial migration is precluded by signals that lead to T cell division. In addition, activation of the transcription factor AP-1, without induction of NF-kappaB, is observed in T cells after noncognate interactions with endothelial cells (EC), a pattern of transcriptional regulation different from that observed in dividing T cells. Up-regulation of certain adhesion (CD11a, CD49d), activation (CD69), and costimulatory (CD86) receptors accompany these transcriptional events. Most importantly, recently migrated T cells display a faster rate of migration when reseeded onto an EC monolayer. Finally, T cells become hyperresponsive to antigenic challenge after noncognate interactions with the endothelium. These effects appear not to be due to the selection of preactivated T lymphocytes, because they occur also in clonal T cell populations and appear to be mediated by alpha(L)beta(2) integrin-CD54 interactions. We conclude that CD4(+) memory T cell extravasation is accompanied by phenotypic and functional changes induced by the interactions with the EC, which favor tissue infiltration by T cells and their further activation once they reach the antigenic site.